Impact of choroid plexus size in prenatal diagnosis of normal and abnormal closure of fourth ventricle.

OBJECTIVE: To assess the role of the choroid plexus (CP) of the fourth ventricle (4V) in fetuses with an open 4V and a normal cerebellar vermis. METHODS: Two groups of patients were recruited in two fetal medicine referral centers. The prospectively collected control group included singleton pregnancies with a normal sonographic examination after first-trimester combined screening for chromosomal abnormalities and normal outcome, recruited in the period between 2019 and 2022. The study group was selected retrospectively by searching our databases to identify all cases with an isolated open 4V and normal anatomy and size of the cerebellar vermis. The inclusion criteria of the study group were: (1) gestational age between 20 and 22 weeks; (2) a brainstem-vermis angle ≥ 18° in the midsagittal plane with an otherwise normal cerebellum and vermis; (3) 4V-CP visible and seen separately from the vermis; (4) absence of other intra- and extracranial anomalies; and (5) available prenatal and/or postnatal magnetic resonance imaging (MRI) data. RESULTS: In 169 cases of the control group, the 4V-CP was seen separately from the cerebellar vermis and was noticed to progressively fill the space caudal to the 4V, between the vermis and brainstem. From 12 to 22 weeks, the surface areas of the vermis and medial portion of the 4V-CP increased progressively with advancing gestation (P < 0.0001). Intra- and interobserver correlation analysis showed good reproducibility for the measurements. Among the cases with an open 4V and a normal vermis, it was retrospectively feasible to visualize the 4V-CP separately from the inferior part of the vermis in 41 fetuses. In five of these cases, the open 4V was due to a small CP. In all 41 fetuses, the diagnosis on MRI was isolated upward rotation of the cerebellar vermis, and no additional anomaly was found. CONCLUSIONS: Closure of the 4V is dependent on the 4V-CP and not only the cerebellar vermis. In fact, a small CP may represent another cause of an open 4V. Therefore, separate visualization of the 4V-CP and cerebellar vermis is crucial to improve discrimination between the different causes of an open 4V at the anomaly scan and its clinical implications. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Pregnancy and perinatal outcomes of early vs late selective termination in dichorionic twin pregnancy: systematic review and meta-analysis.

OBJECTIVE: To evaluate outcomes of dichorionic twin pregnancies undergoing early vs late selective termination of pregnancy (ST). METHODS: MEDLINE, EMBASE, CINAHL and the Web of Science databases were searched electronically up to March 2022. The primary outcome of this study was pregnancy loss prior to 24 weeks' gestation. The secondary outcomes included preterm birth (PTB) before 37, 34, and 32 weeks, preterm prelabor rupture of membranes (PPROM), gestational age (GA) at delivery, Cesarean delivery, mean birth weight, 5-min Apgar score < 7, overall neonatal morbidity and neonatal survival. Only prospective or retrospective studies reporting data on the outcome of early (before 18 weeks) vs late (at or after 18 weeks) ST in dichorionic twin pregnancies were considered suitable for inclusion. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale for cohort studies. Random-effects head-to-head meta-analysis was used to analyze the data. RESULTS: Seven studies reporting on 649 dichorionic twin pregnancies were included in this systematic review. The risk of pregnancy loss prior to 24 weeks was significantly lower in dichorionic twin pregnancies undergoing early compared with late ST (1% vs 8%; odds ratio (OR), 0.25 (95% CI, 0.10-0.65); P = 0.004). The risk of PTB was significantly lower in dichorionic twin pregnancies undergoing early compared with late ST when considering PTB before 37 weeks (19% vs 45%; OR, 0.36 (95% CI, 0.23-0.57); P < 0.00001), before 34 weeks (4% vs 19%; OR, 0.24 (95% CI, 0.11-0.54); P = 0.0005) and before 32 weeks (4% vs 20%; OR, 0.21 (95% CI, 0.05-0.85); P = 0.03). The mean birth weight was significantly greater in the early-ST group (mean difference (MD), 392.2 g (95% CI, 59.1-726.7 g); P = 0.02), as was the mean GA at delivery (MD, 2.47 weeks (95% CI, 0.04-4.91 weeks); P = 0.049). There was no significant difference between dichorionic twin pregnancies undergoing early compared with late ST in terms of PPROM (P = 0.27), Cesarean delivery (P = 0.38), 5-min Apgar score < 7 (P = 0.35) and neonatal survival of the non-reduced twin (P = 0.54). CONCLUSIONS: The risk of pregnancy loss prior to 24 weeks and the rate of PTB before 37, 34 and 32 weeks were significantly higher in dichorionic twin pregnancies undergoing late vs early ST, thus highlighting the importance of early diagnosis of fetal anomalies in twin pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Risk of fetal loss after chorionic villus sampling in twin pregnancy derived from propensity score matching analysis.

OBJECTIVE: To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis. METHODS: This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11-13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial. RESULTS: The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non-CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non-CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (odds ratio (OR), 0.81; 95% CI, 0.48-1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23-0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95-7.13). The effects were statistically significantly different (P-value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non-CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%. CONCLUSION: In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Low torcular Herophili position and large brainstem-tentorium angle in fetuses with open spinal dysraphism at 11-13 weeks' gestation.

OBJECTIVE: To evaluate whether in fetuses with open spina bifida (OSB) the tentorium can be seen to be displaced downwards and vertically oriented by the time of the 11-13-week scan and whether this is reflected in an alteration of the brainstem-tentorium (BST) angle. METHODS: The study population was recruited between 2015 and 2020 from three fetal medicine referral centers and comprised a control group and a study group of pregnancies with OSB. The control group was recruited prospectively and included singleton pregnancies with a normal sonographic examination after first-trimester combined screening for chromosomal abnormalities and normal outcome. The study group was selected retrospectively and included all cases with OSB between 2015 and 2020. All cases underwent detailed ultrasound assessment at 11 + 0 to 13 + 6 weeks' gestation. The position of the torcular Herophili (TH) was identified in the midsagittal view of the fetal brain with the use of color Doppler and was considered as a proxy for the insertion of the tentorium on the fetal skull. The BST angle was calculated in the same view and was compared between the two groups. RESULTS: Sixty normal fetuses were included in the control group and 22 fetuses with OSB in the study group. In both groups, the BST angle was found to be independent of gestational age or crown-rump length (P = 0.8815, R2 = 0.0003861 in the controls, and P = 0.2665, R2 = 0.00978 in the OSB group). The mean BST angle was 48.7 ± 7.8° in controls and 88.1 ± 1.18°, i.e. close to 90°, in fetuses with OSB. Comparison of BST-angle measurements between the control group and cases with OSB showed a statistically significant difference (P = 0.0153). In all fetuses with OSB, the downward displacement of the TH and tentorium was clearly visible at the 11-13-week scan. CONCLUSIONS: In fetuses with OSB, the BST angle is significantly larger than in normal controls, with the tentorium being almost perpendicular to the brainstem. This sign confirms the inferior displacement of the tentorium cerebelli with respect to its normal insertion on the occipital clivus as early as the first trimester of pregnancy and is useful in the diagnosis of Chiari-II malformation at this early stage. In fetuses with OSB, the low position of the tentorium and TH is clearly visible, even subjectively, at the 11-13-week scan. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal loss after chorionic villus sampling in twin pregnancy.

OBJECTIVE: To estimate the chorionic villus sampling (CVS)-related risk of fetal loss in twin pregnancy after adjustment for chorionicity, nuchal translucency thickness (NT), intertwin discordance in crown-rump length (CRL), maternal demographic characteristics and serum pregnancy-associated plasma protein-A (PAPP-A) and free ß-human chorionic gonadotropin (ß-hCG). METHODS: This was a multicenter study from eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. Data were obtained prospectively from women with twin pregnancy undergoing routine ultrasound examination at 11-13 weeks' gestation. Multivariable logistic regression analysis with backward stepwise elimination was used to examine whether CVS provided a significant independent contribution to the prediction of risk of fetal loss after adjusting for maternal and pregnancy characteristics, including maternal age, racial origin and weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥ 95th percentile and free ß-hCG and PAPP-A multiples of the median. Similarly, within the CVS group, multivariable logistic regression analysis was used to investigate the effect of the number of intrauterine needle insertions and size of the needle on the risk of fetal loss. RESULTS: The study population of 8581 twin pregnancies undergoing ultrasound examination at 11-13 weeks' gestation included 316 dichorionic and 129 monochorionic twins that had CVS. First, in twin pregnancies undergoing CVS, compared to those not undergoing CVS, there was a 2-fold increased risk of fetal loss at < 24 weeks' gestation and of loss at any stage in pregnancy. Second, the factors providing a significant independent contribution to the prediction of miscarriage or fetal loss in twin pregnancy were increased maternal weight, black racial origin, monochorionicity, and more so monoamnionicity, large intertwin discordance in CRL and increased fetal NT, and, in the case of fetal loss at any stage, there was also a contribution from assisted conception and low serum PAPP-A. Third, after adjustment for maternal and pregnancy characteristics, CVS did not provide a significant contribution to the risk of fetal loss. Fourth, in twin pregnancies that had CVS, there was no significant contribution to fetal loss from the number of intrauterine needle insertions or needle size. CONCLUSION: The 2-fold increased risk of fetal loss following CVS in twin pregnancy can, to a great extent, be explained by maternal and pregnancy characteristics rather than the invasive procedure itself. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Position of the choroid plexus of the fourth ventricle in first- and second-trimester fetuses: a novel approach to early diagnosis of cystic posterior fossa anomalies.

OBJECTIVE: To describe the sonographic appearance and position of the choroid plexus of the fourth ventricle (4V-CP) between 12 and 21 weeks' gestation in normal fetuses and in fetuses with Dandy-Walker malformation (DWM) or Blake's pouch cyst (BPC). METHODS: The study population comprised 90 prospectively recruited normal singleton pregnancies and 41 pregnancies identified retrospectively from our institutional database that had a suspected posterior fossa anomaly at 12-13 weeks' gestation based on the ultrasound finding of abnormal hindbrain spaces. In all cases the final diagnosis was confirmed by prenatal and/or postnatal magnetic resonance imaging or postmortem examination. All pregnancies underwent a detailed ultrasound assessment, including a dedicated examination of the posterior fossa, at 12-13 weeks, 15-16 weeks and 20-21 weeks of gestation. Two-dimensional ultrasound images of the midsagittal and coronal views of the brain through the posterior fontanelle and three-dimensional volume datasets were obtained. Multiplanar orthogonal image correlation with volume contrast imaging was used as the reference visualization mode. Two independent operators, blinded to the fetal outcome, were asked to classify the 4V-CP as visible or not visible in both normal and abnormal cases, and to assess if the 4V-CP was positioned inside or outside the cyst in fetuses with DWM and BPC. RESULTS: Of the 41 fetuses with apparently isolated cystic posterior fossa anomaly in the first trimester, eight were diagnosed with DWM, 29 were diagnosed with BPC and four were found to be normal in the second trimester. The position of the 4V-CP differed between DWM, BPC and normal cases in the first- and second-trimester ultrasound examinations. In particular, in normal fetuses, no cyst was present and, in the midsagittal and coronal planes of the posterior fossa, the 4V-CP appeared as an echogenic oval-shaped structure located inside the 4V apparently attached to the cerebellar vermis. In fetuses with DWM, the 4V-CP was not visible in the midsagittal view because it was displaced inferolaterally by the cyst. In contrast, in the coronal view of the posterior brain, the 4V-CP was visualized in all cases with DWM at 12-13 weeks, with a moderate decrease in the visualization rate at 15-16 weeks (87.5%) and at 20-21 weeks (75%). In the coronal view, the 4V-CP was classified as being outside the cyst in all DWM cases at 12-13 weeks and in 87.5% and 75% of cases at 15-16 and 20-21 weeks, respectively. In fetuses with BPC, the 4V-CP was visualized in all cases in both the midsagittal and coronal views at 12-13 weeks and in 100% and 96.6% of cases, respectively, at 15-16 weeks. In the coronal view, the 4V-CP was classified as being inside the cyst in 28 (96.6%), 27 (93.1%) and 25 (86.2%) cases at 12-13, 15-16 and 20-21 weeks, respectively. The medial segment of the 4V-CP was visualized near the inferior part of the vermis. CONCLUSIONS: Our study shows that longitudinal ultrasound assessment of the 4V-CP and its temporal changes from 12 to 21 weeks is feasible. The 4V-CP is located inside the cyst, just below the vermis, in BPC and outside the cyst, inferolaterally displaced and distant from the vermian margin, in DWM, consistent with the pathogenesis of the two conditions. The position of the 4V-CP is a useful sonographic marker that can help differentiate between DWM and BPC as early as in the first trimester of pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Percutaneous fetoscopic spina bifida repair: effect on ambulation and need for postnatal cerebrospinal fluid diversion and bladder catheterization.

OBJECTIVE: A trial comparing prenatal with postnatal open spina bifida (OSB) repair established that prenatal surgery was associated with better postnatal outcome. However, in the trial, fetal surgery was carried out through hysterotomy. Minimally invasive approaches are being developed to mitigate the risks of open maternal-fetal surgery. The objective of this study was to investigate the impact of a novel neurosurgical technique for percutaneous fetoscopic repair of fetal OSB, the skin-over-biocellulose for antenatal fetoscopic repair (SAFER) technique, on long-term postnatal outcome. METHODS: This study examined descriptive data for all patients undergoing fetoscopic OSB repair who had available 12- and 30-month follow-up data for assessment of need for cerebrospinal fluid (CSF) diversion and need for bladder catheterization and ambulation, respectively, from eight centers that perform prenatal OSB repair via percutaneous fetoscopy using a biocellulose patch between the neural placode and skin/myofascial flap, without suture of the dura mater (SAFER technique). Univariate and multivariate logistic regression analyses were used to examine the effect of different factors on need for CSF diversion at 12 months and ambulation and need for bladder catheterization at 30 months. Potential cofactors included gestational age at fetal surgery and delivery, preoperative ultrasound findings of anatomical level of the lesion, cerebral lateral ventricular diameter, lesion type and presence of bilateral talipes, as well as postnatal findings of CSF leakage at birth, motor level, presence of bilateral talipes and reversal of hindbrain herniation. RESULTS: A total of 170 consecutive patients with fetal OSB were treated prenatally using the SAFER technique. Among these, 103 babies had follow-up at 12 months of age and 59 had follow-up at 30 months of age. At 12 months of age, 53.4% (55/103) of babies did not require ventriculoperitoneal shunt or third ventriculostomy. At 30 months of age, 54.2% (32/59) of children were ambulating independently and 61.0% (36/59) did not require chronic intermittent catheterization of the bladder. Multivariate logistic regression analysis demonstrated that significant prediction of need for CSF diversion was provided by lateral ventricular size and type of lesion (myeloschisis). Significant predictors of ambulatory status were prenatal bilateral talipes and anatomical and functional motor levels of the lesion. There were no significant predictors of need for bladder catheterization. CONCLUSION: Children who underwent prenatal OSB repair via the percutaneous fetoscopic SAFER technique achieved long-term neurological outcomes similar to those reported in the literature after hysterotomy-assisted OSB repair. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Maternal exposure to air pollutants, PCSK9 levels, fetal growth and gestational age - An Italian cohort.

OBJECTIVE: Exposure to airborne pollutants during pregnancy appears to be associated with uterine growth restriction and adverse neonatal outcome. Proprotein convertase subtilisin/kexin type (PCSK9), the key modulator of low-density lipoprotein (LDL) metabolism, increases following particulate matter (PM10) exposure. Because maternal cholesterol is required for fetal growth, PCSK9 levels could be used to evaluate the potential impact of airborne pollutants on fetal growth. DESIGN: A cohort of 134 healthy women during early pregnancy (11-12 weeks of gestational age) was studied. RESULTS: A significant association between circulating PCSK9 levels and three tested air pollutants (PM10, PM2.5, nitric oxide (NO2)) was found. Of importance, gestational age at birth was reduced by approximately 1 week for each 100 ng/mL rise in circulating PCSK9 levels, an effect that became more significant at the highest quartile of PM2.5 (with a 1.8 week advance in delivery date for every 100 ng/mL rise in circulating PCSK9; p for interaction = 0.026). This finding was supported by an elevation of the odds ratio for urgent cesarean delivery for each 100 ng/mL rise in PCSK9 (2.99, 95% CI, 1.22-6.57), similar trends being obtained for PM10 and NO2. CONCLUSIONS: The association between exposure to air pollutants during pregnancy and elevation in PCSK9 advances our understanding of the unforeseen influences of environmental exposure in terms of pregnancy associated disorders.

Role of magnetic resonance imaging in fetuses with mild or moderate ventriculomegaly in the era of fetal neurosonography: systematic review and meta-analysis.

OBJECTIVES: To report the rate of additional central nervous system (CNS) anomalies detected exclusively on prenatal magnetic resonance imaging (MRI) in fetuses diagnosed with isolated mild or moderate ventriculomegaly (VM) on ultrasound, according to the type of ultrasound protocol adopted (dedicated neurosonography vs standard assessment of the fetal brain), and to explore whether the diagnostic performance of fetal MRI in detecting such anomalies is affected by gestational age at examination and laterality and degree of ventricular dilatation. METHODS: MEDLINE, EMBASE, CINAHL and Clinicaltrials.gov were searched for studies reporting on the prenatal MRI assessment of fetuses diagnosed with isolated mild or moderate VM (ventricular dilatation of 10-15 mm) on ultrasound. Additional anomalies detected only on MRI were classified as callosal, septal, posterior fossa, white matter, intraventricular hemorrhage, cortical, periventricular heterotopia, periventricular cysts or complex malformations. The rate of additional anomalies was compared between fetuses diagnosed on dedicated neurosonography, defined as a detailed assessment of the fetal brain, according to the International Society of Ultrasound in Obstetrics and Gynecology guidelines, and those diagnosed on standard fetal brain assessment. The rate of additional CNS anomalies missed on prenatal MRI and detected only at birth was calculated and compared between fetuses that had early (at or before 24 weeks' gestation) and those that had late (after 24 weeks) MRI. Subanalysis was performed according to the laterality (uni- vs bilateral) and degree (mild vs moderate, defined as ventricular dilatation of 10-12 and 13-15 mm, respectively) of ventricular dilatation. Whether MRI assessment led to a significant change in prenatal management was explored. Random-effects meta-analysis of proportions was used. RESULTS: Sixteen studies (1159 fetuses) were included in the systematic review. Overall, MRI detected an anomaly not identified on ultrasound in 10.0% (95% CI, 6.2-14.5%) of fetuses. However, when stratifying the analysis according to the type of ultrasound assessment, the rate of associated anomalies detected only on MRI was 5.0% (95% CI, 3.0-7.0%) when dedicated neurosonography was performed compared with 16.8% (95% CI, 8.3-27.6%) in cases that underwent a standard assessment of the fetal brain in the axial plane. The overall rate of an additional anomaly detected only at birth and missed on prenatal MRI was 0.9% (95% CI, 0.04-1.5%) (I2 , 0%). There was no difference in the rate of an associated anomaly detected only after birth when fetal MRI was carried out before, compared with after, 24 weeks of gestation (P = 0.265). The risk of detecting an associated CNS abnormality on MRI was higher in fetuses with moderate than in those with mild VM (odds ratio, 8.1 (95% CI, 2.3-29.0); P = 0.001), while there was no difference in those presenting with bilateral, compared with unilateral, dilatation (P = 0.333). Finally, a significant change in perinatal management, mainly termination of pregnancy owing to parental request, following MRI detection of an associated anomaly, was observed in 2.9% (95% CI, 0.01-9.8%) of fetuses undergoing dedicated neurosonography compared with 5.1% (95% CI, 3.2-7.5%) of those having standard assessment. CONCLUSIONS: In fetuses undergoing dedicated neurosonography, the rate of a CNS anomaly detected exclusively on MRI is lower than that reported previously. Early MRI has an excellent diagnostic performance in identifying additional CNS anomalies, although the findings from this review suggest that MRI performed in the third trimester may be associated with a better detection rate for some types of anomaly, such as cortical, white matter and intracranial hemorrhagic anomalies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Particulate Air Pollution, Blood Mitochondrial DNA Copy Number, and Telomere Length in Mothers in the First Trimester of Pregnancy: Effects on Fetal Growth.

Growing evidences have shown that particulate matter (PM) exposures during pregnancy are associated with impaired fetal development and adverse birth outcomes, possibly as a result of an exaggerated systemic oxidative stress and inflammation. Telomere length (TL) is strongly linked to biological age and is impacted by oxidative stress. We hypothesized that PM exposure during different time windows in the first trimester of pregnancy influences both mitochondrial DNA copy number (mtDNAcn), an established biomarker for oxidative stress, and TL. Maternal blood TL and mtDNAcn were analysed in 199 healthy pregnant women recruited at the 11th week of pregnancy by quantitative polymerase chain reaction. We also examined whether maternal mtDNAcn and TL were associated with fetal growth outcomes measured at the end of the first trimester of pregnancy (fetal heart rate, FHR; crown-rump length, CRL; and nuchal translucency, NT) and at delivery (birth weight, length, head circumference). The possible modifying effect of prepregnancy maternal body mass index was evaluated. PM10 exposure during the first pregnancy trimester was associated with an increased maternal mtDNAcn and a reduced TL. As regards ultrasound fetal outcomes, both FHR and CRL were positively associated with PM2.5, whereas the association with FHR was confirmed only when examining PM10 exposure. PM10 was also associated with a reduced birth weight. While no association was found between mtDNAcn and CRL, we found a negative relationship between mtDNAcn and fetal CRL only in overweight women, whereas normal-weight women exhibited a positive, albeit nonsignificant, association. As abnormalities of growth in utero have been associated with postnatal childhood and adulthood onset diseases and as PM is a widespread pollutant relevant to the large majority of the human population and obesity a rising risk factor, our results, if confirmed in a larger population, might represent an important contribution towards the development of more targeted public health strategies.

Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation.

OBJECTIVE: To examine the performance of screening for early, preterm and term pre-eclampsia (PE) at 11-13 weeks' gestation by maternal factors and combinations of mean arterial pressure (MAP), uterine artery (UtA) pulsatility index (PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A). METHODS: The data for this study were derived from three previously reported prospective non-intervention screening studies at 11 + 0 to 13 + 6 weeks' gestation in a combined total of 61 174 singleton pregnancies, including 1770 (2.9%) that developed PE. Bayes' theorem was used to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics, with various combinations of biomarker multiples of the median (MoM) values to derive patient-specific risks of delivery with PE at < 37 weeks' gestation. The performance of such screening was estimated. RESULTS: In pregnancies that developed PE, compared to those without PE, the MoM values of UtA-PI and MAP were increased and those of PAPP-A and PlGF were decreased, and the deviation from normal was greater for early than late PE for all four biomarkers. Combined screening by maternal factors, UtA-PI, MAP and PlGF predicted 90% of early PE, 75% of preterm PE and 41% of term PE, at a screen-positive rate of 10%; inclusion of PAPP-A did not improve the performance of screening. The performance of screening depended on the racial origin of the women; on screening by a combination of maternal factors, MAP, UtA-PI and PlGF and using a risk cut-off of 1 in 100 for PE at < 37 weeks in Caucasian women, the screen-positive rate was 10% and detection rates for early, preterm and term PE were 88%, 69% and 40%, respectively. With the same method of screening and risk cut-off in women of Afro-Caribbean racial origin, the screen-positive rate was 34% and detection rates for early, preterm and term PE were 100%, 92% and 75%, respectively. CONCLUSION: Screening by maternal factors and biomarkers at 11-13 weeks' gestation can identify a high proportion of pregnancies that develop early and preterm PE. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG.

Prediction and prevention of small-for-gestational-age neonates: evidence from SPREE and ASPRE.

OBJECTIVES: To examine the effect of first-trimester screening for pre-eclampsia (PE) on the prediction of delivering a small-for-gestational-age (SGA) neonate and the effect of prophylactic use of aspirin on the prevention of SGA. METHODS: The data for this study were derived from two multicenter studies. In SPREE, we investigated the performance of screening for PE by a combination of maternal characteristics and biomarkers at 11-13 weeks' gestation. In ASPRE, women with a singleton pregnancy identified by combined screening as being at high risk for preterm PE (> 1 in 100) participated in a trial of aspirin (150 mg/day from 11-14 until 36 weeks' gestation) compared to placebo. In this study, we used the data from the ASPRE trial to estimate the effect of aspirin on the incidence of SGA with birth weight < 10th , < 5th and < 3rd percentile for gestational age. We also used the data from SPREE to estimate the proportion of SGA in the pregnancies with a risk for preterm PE of > 1 in 100. RESULTS: In SPREE, screening for preterm PE by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index and serum placental growth factor identified a high-risk group that contained about 46% of SGA neonates < 10th percentile born at < 37 weeks' gestation (preterm) and 56% of those born at < 32 weeks (early); the overall screen-positive rate was 12.2% (2014 of 16 451 pregnancies). In the ASPRE trial, use of aspirin reduced the overall incidence of SGA < 10th percentile by about 40% in babies born at < 37 weeks' gestation and by about 70% in babies born at < 32 weeks; in babies born at ≥ 37 weeks, aspirin did not have a significant effect on incidence of SGA. The aspirin-related decrease in incidence of SGA was mainly due to its incidence decreasing in pregnancies with PE, for which the decrease was about 70% in babies born at < 37 weeks' gestation and about 90% in babies born at < 32 weeks. On the basis of these results, it was estimated that first-trimester screening for preterm PE and use of aspirin in the high-risk group would potentially reduce the incidence of preterm and early SGA by about 20% and 40%, respectively. CONCLUSION: First-trimester screening for PE by the combined test identifies a high proportion of cases of preterm SGA that can be prevented by the prophylactic use of aspirin. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG.

Prospective comparative study of characteristics associated with influenza A and B in adults.

OBJECTIVES: To describe and compare the epidemiological characteristics associated with influenza type A and B as well as the characteristics associated with influenza pneumonia. The secondary objective was to evaluate the performance of influenza rapid diagnostic tests (RDT) in the emergency department. PATIENTS AND METHODS: Prospective study, including 251 adult patients admitted to the emergency department during the 2013-2014 influenza outbreaks for flu-like illness confirmed by RT-PCR. RESULTS: A total of 106 patients were infected with influenza type B (42%) and 145 with influenza type A (58%). Mean age was 56 and the sex-ratio was 0.9. In a multivariate analysis, the only factor independently related with the type of influenza strain was the patient's age. Overall, 17% of influenza-infected patients were vaccinated and 38% presented with pneumonia, with no significant difference between strains. In a univariate analysis, the risk factors associated with the occurrence of pneumonia were age, vaccination, and chronic obstructive pulmonary disease. Only 22% of samples positive by RT-PCR for influenza B and 40% for influenza A were positive by RDT. CONCLUSION: Influenza type A and type B had similar clinical and biological signs, including severity. Influenza type B should not be neglected. Any emergency department may use the RDT for its ease-of-use and rapidity. However, its low sensitivity should be taken into consideration when interpreting results.

ASPRE trial: performance of screening for preterm pre-eclampsia.

OBJECTIVE: To examine the performance of screening for preterm and term pre-eclampsia (PE) in the study population participating in the ASPRE (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) trial. METHODS: This was a prospective first-trimester multicenter study on screening for preterm PE in 26 941 singleton pregnancies by means of an algorithm that combines maternal factors, mean arterial pressure, uterine artery pulsatility index and maternal serum pregnancy-associated plasma protein-A and placental growth factor at 11-13 weeks' gestation. Eligible women with an estimated risk for preterm PE of > 1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg per day) vs placebo from 11-14 until 36 weeks' gestation, which showed that, in the aspirin group, the incidence of preterm PE was reduced by 62%. In the screened population, the detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 37 and ≥ 37 weeks were estimated after adjustment for the effect of aspirin in those receiving this treatment. We excluded 1144 (4.2%) pregnancies because of loss to follow-up or study withdrawal (n = 716), miscarriage (n = 243) or termination (n = 185). RESULTS: The study population of 25 797 pregnancies included 180 (0.7%) cases of preterm PE, 450 (1.7%) of term PE and 25 167 (97.6%) without PE. In combined first-trimester screening for preterm PE with a risk cut-off of 1 in 100, the DR was 76.7% (138/180) for preterm PE and 43.1% (194/450) for term PE, at screen-positive rate of 10.5% (2707/25 797) and FPR of 9.2% (2375/25 797). CONCLUSION: The performance of screening in the ASPRE study was comparable with that of a study of approximately 60 000 singleton pregnancies used for development of the algorithm; in that study, combined screening detected 76.6% of cases of preterm PE and 38.3% of term PE at a FPR of 10%. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation.

OBJECTIVE: To examine the diagnostic accuracy of a previously developed model for prediction of pre-eclampsia (PE) by a combination of maternal factors and biomarkers at 11-13 weeks' gestation. METHODS: This was a prospective first-trimester multicenter study of screening for PE in 8775 singleton pregnancies. A previously published algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those for the dataset used for development of the algorithm. RESULTS: In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. With combined screening by maternal factors, mean arterial pressure, uterine artery pulsatility index and serum placental growth factor, the DR was 100% (95% CI, 80-100%) for PE < 32 weeks, 75% (95% CI, 62-85%) for PE < 37 weeks and 43% (95% CI, 35-50%) for PE ≥ 37 weeks, at a 10% FPR. These DRs were similar to the estimated rates for the dataset used for development of the model: 89% (95% CI, 79-96%) for PE < 32 weeks, 75% (95% CI, 70-80%) for PE < 37 weeks and 47% (95% CI, 44-51%) for PE ≥ 37 weeks. CONCLUSION: Assessment of a combination of maternal factors and biomarkers at 11-13 weeks provides effective first-trimester screening for preterm PE. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

New minimally invasive technique for cystoscopic laser treatment of fetal ureterocele.

Prenatal ultrasound detection of fetal ureterocele with bilateral hydroureteronephrosis, obstruction of the bladder outlet and progressive amniotic fluid reduction have been associated with a significant risk of end-stage chronic renal disease after birth. Fetal cystoscopic laser incision of the ureterocele, using standard 3.5-mm fetoscopic access to the amniotic cavity and the fetal bladder with the aim of relieving the bladder outflow obstruction to preserve renal function, has been reported previously in a case with a favorable outcome. We report on two additional cases of fetal ureterocele treated by cystoscopic laser decompression. In the first case, a standard 3.3-mm uterine entry was used. In the second case, a new approach was adopted using an 'all-seeing needle' 1.6-mm endoscope. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Sphenofrontal distance on three-dimensional ultrasound in euploid and trisomy-21 fetuses at 16-24 weeks' gestation.

OBJECTIVE: To compare the distance between the sphenoid and frontal bones on three-dimensional (3D) ultrasound in euploid and trisomy-21 fetuses at 16-24 weeks' gestation. METHODS: We acquired 3D volumes of the fetal profile from 80 normal and 30 trisomy-21 fetuses at 16-24 weeks' gestation. We used the multiplanar mode to obtain the mid-sagittal plane and measured the sphenofrontal distance as the shortest distance between the most anterior edge of the sphenoid bone and the lowest edge of the frontal bone. RESULTS: In normal fetuses, the sphenofrontal distance increased linearly with gestational age, from 15.1 mm at 16 weeks to 18.2 mm at 24 weeks. In fetuses with trisomy 21, the mean sphenofrontal distance delta value was significantly smaller than in normal cases (-3.447 mm (95% CI, -5.684 to -1.211 mm); P < 0.01). The sphenofrontal distance was below the 5(th) and 1(st) percentiles of the normal range in 29 (96.7%) and 27 (90.0%) trisomy-21 fetuses, respectively. CONCLUSIONS: The sphenofrontal distance is shorter at 16-24 weeks' gestation in fetuses with trisomy 21 than in normal fetuses. A reduction in the growth of the anterior cranial base contributes to the mid-facial hypoplasia observed in fetuses with trisomy 21. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

[SECOND STAGE IN MINIINVASIVE FETAL SURGERY FOR SEVERE CONGENITAL DIAPHRAGMATIC HERNIA. CASE REPORT].

We present a case of miniinvasive fetal surgery for CDH treated at 28 and 34 weeks of gestation. The first step was successfully performed at 28 weeks with Fetal Endoscopic Tracheal Occlusion with ballon. The second step was performed at 34 weeks for balloon removal. The necessity of fetal cytogenetic assessment and array CGH was carried out to exclude gene disorders that could lead to poor long-term outcome. A planned SC and optimal neonatology management were followed by a surgical operation of the newborn. Experienced interdisciplinary team successfully provide a perinatal and postnatal surgery for severe CDH. The newborn was discharged from the hospital 3 weeks after the repairing operation in a good condition.